Recurrence after neoadjuvant chemoradiation and surgery for esophageal cancer: does the pattern of recurrence differ for patients with complete response and those with partial or no response?

Abstract

Objective: We hypothesized that most relapses in patients with esophageal cancer having neoadjuvant chemoradiation therapy would occur outside of the surgical and radiation fields.

Methods: Recurrence patterns, time to recurrence, and median survival were examined in 267 patients who had esophagectomy after neoadjuvant chemoradiation therapy at Johns Hopkins over 19 years.

Results: Of 267 patients, 82 (30.7%) showed complete response to neoadjuvant therapy, with 108 (40.4%) and 77 (28.8%) showing partial response or no response, respectively. Recurrence developed in 84 patients (patients with complete response 18/82, 21.4%; patients with partial response 39/108, 36.1%; patients with no response 27/77, 35.1%; P = .055, respectively). Most patients had recurrences at distant sites (65/84;77.4%) regardless of pathologic response, and subsequent survival was brief (median 8.37 months). Median disease-free survival was short (10 months) and did not differ based on recurrence site for patients with partial response or no response, but was longer for patients with complete response with distant recurrence, whose median disease-free survival was 27.3 months (P = .008). By multivariate analysis, no other factor except for pathologic response to neoadjuvant therapy was associated with disease recurrence or death. Patients with partial response or no response were 1.97 and 2.23 times more likely to have recurrence than patients with complete response (P = .024 and P = .012, respectively).

Conclusions: Most esophageal cancer recurrences after neoadjuvant therapy and surgery are distant, and survival time after recurrence is short regardless of pathologic response. Fewer patients achieving complete response had recurrences, and distant recurrences in these patients manifest later than in patients showing partial response and those showing no response. Only pathologic response is significantly associated with disease recurrence, suggesting that tumor biology and chemosensitivity are critical in long-term patient outcome.

Figure 1

Kaplan-Meier Estimates of Recurrence-Free Survival of Esophageal Cancer Patients (n=261) at the Johns Hopkins Hospital, according to Pathological Response at Time of Surgical Resection.

Figure 2

Kaplan-Meier Estimates of Overall Survival of Esophageal Cancer Patients (n=267) at the Johns Hopkins Hospital, according to Pathological Response at Time of Surgical Resection. The Kaplan-Meier estimates for overall survival indicate that as the extent of pathological response to neoadjuvant therapy increases, there is a significant increase in the overall survival of the patient. It is interesting to note, however, that in our observed cohort, the degree of pathological response to neoadjuvant therapy seemed not to affect patients with early mortality (<10 months) but rather those who survived more than one year.

Figure 3

Kaplan-Meier Estimates of Overall Survival of Esophageal Cancer Patients who had a complete pathological response to neoadjuvant therapy (n=82) at the Johns Hopkins Hospital, according to whether or not there was cancer recurrence following surgical resection.

Figure 4

Kaplan-Meier Estimates of Overall Survival of Esophageal Cancer Patients who had a partial pathological response to neoadjuvant therapy (n=108) at the Johns Hopkins Hospital, according to whether or not there was cancer recurrence following surgical resection.

Figure 5

Kaplan-Meier Estimates of Overall Survival of Esophageal Cancer Patients who had no pathological response to neoadjuvant therapy (n=71) at the Johns Hopkins Hospital, according to whether or not there was cancer recurrence following surgical resection.